Cancer is the second leading cause of death in the United States today. By the time a solid tumor cancer is clinically detectable, a tumor may be several centimeters in diameter and spread to other organs. Removal of the primary tumor may stimulate tumors to enter a phase of rapid growth and initiate their own vasculature. This rapid growth of secondary tumors may be due to the result of a cancer cell's own resistance to apoptosis.
Apoptotic cell death via the FAS-mediated system provides balanced cell proliferation and renewal with cell turnover. Cancer cells have developed a number of biological mechanisms to avoid apoptosis. For example, lung and colon cancer cells secrete elevated levels of soluble “decoy” molecules that bind to FasL, thereby inhibiting its binding to Fas. A cancer cell can also resist the effects of FAS-mediated apoptosis by expressing one or more of its own intracellular inhibitory molecules that bind to an intermediate protein of FAS-mediated apoptosis.
While potential cancer therapeutic compounds have been identified that modulate FAS-mediated apoptosis, these compounds have proven to not be effective in slowing tumor growth at a fast enough rate for reducing the probability of metastasis. Accordingly, there remains a need for methods which can effectively screen for modulators of apoptosis.